1373554-61-0Relevant articles and documents
Synthesis of 2-anilinopyridine dimers as microtubule targeting and apoptosis inducing agents
Kamal, Ahmed,Ali Hussaini,Lakshma Nayak,Shaheer Malik,Lakshmi Sucharitha,Shaik, Thokhir Basha,Ashraf, Md.,Bagul, Chandrakant
, p. 6755 - 6767 (2014)
A series of 2-anilinopyridine dimers have been synthesized and evaluated for their anticancer potential. Most of the compounds have showed significant growth inhibition of the cell lines tested and compound 4d was most effective amongst the series display
Design, synthesis and antiproliferative activity of the new conjugates of E7010 and resveratrol as tubulin polymerization inhibitors
Kamal, Ahmed,Ashraf,Basha, Shaik Thokhir,Ali Hussaini,Singh, Shamshair,Vishnuvardhan,Kiran, Boppana,Sridhar, Balasubramanian
, p. 1382 - 1394 (2016/02/03)
A new class of (E)-N-phenyl-3-styrylpyridin-2-amine conjugates were designed and synthesized on the basis of E7010 and resveratrol scaffolds. These conjugates were evaluated for their antiproliferative activity in four human cancer cell lines with GI50 values ranging from 2.1 μM to 20 μM. Two of the conjugates RSV-1 and RSV-11 were found to possess 13-fold higher GI50 values than resveratrol and 1 to 2 fold higher GI50 values than E7010 against the human cervical HepG2 cancer line. They displayed high potency and selectivity in a panel of NCI 60 human cancer cell lines. Based on the GI50 values against the panel of 60 NCI cancer cell lines and dock scores from the molecular modelling studies, we selected RSV-1 and RSV-11 for tubulin polymerization and mechanistic studies. Furthermore, RSV-1 and RSV-11 compounds inhibited the assembly of tubulin by strongly binding to the colchicine-binding site. The G2/M-phase is arrested in HepG2 cells as assessed by flow cytometry. Structure based studies, western blotting and immunofluorescence experiments demonstrated that RSV-1 and RSV-11 depolymerize microtubules in the HepG2 cell line, resulting in an accumulation of G2/M cells.
Synthesis of 2-anilinopyridyl-triazole conjugates as antimitotic agents
Kamal, Ahmed,Subba Rao,Vishnuvardhan,Srinivas Reddy,Swapna, Konderu,Bagul, Chandrakant,Subba Reddy,Srinivasulu, Vunnam
, p. 4879 - 4895 (2015/05/05)
A series of 2-anilinopyridyl-triazole conjugates (6a-t) were prepared and evaluated for their cytotoxic activity against a panel of three human cancer cell lines. Among them compounds 6q, 6r and 6s showed significant cytotoxic activity with IC50 values ranging from 0.1 to 4.1 μM. Structure-activity relationships were elucidated with various substitutions on these conjugates. Flow cytometric analysis revealed that these compounds arrest the cell cycle at the G2/M phase and induce cell death by apoptosis. The tubulin polymerization assay and immunofluorescence analysis showed that these compounds (6q, 6r and 6s) effectively inhibited the microtubule assembly in human prostate cancer cells (DU-145). The docking studies showed that 6s interacts and binds efficiently with the tubulin protein at the colchicine binding site. This was further confirmed by the colchicine competitive binding assay. Moreover, compounds 6q, 6r and 6s possess anti-tubulin activity both in vitro and within cells as demonstrated by the ratio of soluble versus polymerized tubulin. Further the apoptotic effects of compounds were confirmed by Hoechst staining, caspase 3 activation, annexin-V FITC, mitochondrial membrane potential and DNA fragmentation analysis. Interestingly, these compounds did not affect the normal human embryonic kidney cells, HEK-293.
